In Vitro Fabrication of Microscale Secretory Granules
Por:
Lopez-Laguna, H, Parlade, E, Alamo, P, Sanchez, JM, Volta-Duran, E, Serna, N, Sanchez-Garcia, L, Cano-Garrido, O, Sanchez-Chardi, A, Villaverde, A, Mangues, R, Unzueta, U, Vazquez, E
Publicada:
1 may 2021
Ahead of Print:
1 mar 2021
Resumen:
Advanced medical treatments involving drug delivery require fully biocompatible materials with the ability to release functional drugs in a time-prolonged way. Ideally, the delivered molecules should be self-contained as chemically homogenous entities to prevent the use of potentially toxic scaffolds or hold matrices. In nature, peptidic hormones are self-stored in protein-only secretory granules formed by the reversible coordination of Zn2+ and histidine residues. Inspired by this concept, an in vitro transversal procedure is developed, analyzed, and comparatively applied for the fabrication of protein-only secretory granules at the microscale. These materials can be produced from any polyhistidine-tagged protein using physiological concentrations of Zn2+ as a potent and versatile glue-like agent. The screening of granules formed by 12 engineered and nonengineered proteins at different Zn2+ concentrations revealed optimal fabrication conditions and the consequent release profiles. Moreover, the functional and structural properties of the delivered protein are fully validated using a drug-targeting protein platform in a mouse model of human colorectal cancer. In summary, short histidine tags allow the packaging of structurally and functionally dissimilar polypeptides, which supports the proposed fabrication method as a powerful protocol extensible to diverse clinical scenarios in which slow protein drug delivery is required.
Filiaciones:
Lopez-Laguna, H:
Univ Autonoma Barcelona, Inst Biotecnol Biomed, Bellaterra 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
CIBER Bioingenieria, Biomateri Nanomed CIBER BBN, C Monforte Lemos 3-5, Madrid 28029, Spain
Parlade, E:
Univ Autonoma Barcelona, Inst Biotecnol Biomed, Bellaterra 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
CIBER Bioingenieria, Biomateri Nanomed CIBER BBN, C Monforte Lemos 3-5, Madrid 28029, Spain
Alamo, P:
Univ Autonoma Barcelona, Inst Biotecnol Biomed, Bellaterra 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
CIBER Bioingenieria, Biomateri Nanomed CIBER BBN, C Monforte Lemos 3-5, Madrid 28029, Spain
Inst Invest Biomed St Pau IIB St Pau, Sant Antoni Ma Claret 167, Barcelona 08025, Spain
Inst Invest Leucemia Josep Carreras, Barcelona 08025, Spain
Sanchez, JM:
Univ Autonoma Barcelona, Inst Biotecnol Biomed, Bellaterra 08193, Spain
Univ Nacl Cordoba, Inst Invest Biol & Tecnol IIBYT, CONICET, ICTA, Av Velez Sarsfield 1611,X 5016GCA, Cordoba, Argentina
UNC, FCEFyN, Dept Quim, Catedra Quim Biol, Av Velez Sarsfield 1611,X 5016GCA, Cordoba, Argentina
Volta-Duran, E:
Univ Autonoma Barcelona, Inst Biotecnol Biomed, Bellaterra 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
CIBER Bioingenieria, Biomateri Nanomed CIBER BBN, C Monforte Lemos 3-5, Madrid 28029, Spain
Serna, N:
Univ Autonoma Barcelona, Inst Biotecnol Biomed, Bellaterra 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
CIBER Bioingenieria, Biomateri Nanomed CIBER BBN, C Monforte Lemos 3-5, Madrid 28029, Spain
Sanchez-Garcia, L:
Univ Autonoma Barcelona, Inst Biotecnol Biomed, Bellaterra 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
CIBER Bioingenieria, Biomateri Nanomed CIBER BBN, C Monforte Lemos 3-5, Madrid 28029, Spain
Cano-Garrido, O:
Univ Autonoma Barcelona, Nanoligent SL, Edifici Eureka, Barcelona 08193, Spain
Sanchez-Chardi, A:
Univ Autonoma Barcelona, Serv Microscopia, Barcelona 08193, Spain
Univ Barcelona, Fac Biol, Dept Biol Evolut Ecol & Ciencies Ambientals, Av Diagonal 643, Barcelona 08028, Spain
Villaverde, A:
Univ Autonoma Barcelona, Inst Biotecnol Biomed, Bellaterra 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
CIBER Bioingenieria, Biomateri Nanomed CIBER BBN, C Monforte Lemos 3-5, Madrid 28029, Spain
Mangues, R:
CIBER Bioingenieria, Biomateri Nanomed CIBER BBN, C Monforte Lemos 3-5, Madrid 28029, Spain
Inst Invest Biomed St Pau IIB St Pau, Sant Antoni Ma Claret 167, Barcelona 08025, Spain
Inst Invest Leucemia Josep Carreras, Barcelona 08025, Spain
Unzueta, U:
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
CIBER Bioingenieria, Biomateri Nanomed CIBER BBN, C Monforte Lemos 3-5, Madrid 28029, Spain
Inst Invest Biomed St Pau IIB St Pau, Sant Antoni Ma Claret 167, Barcelona 08025, Spain
Inst Invest Leucemia Josep Carreras, Barcelona 08025, Spain
Vazquez, E:
Univ Autonoma Barcelona, Inst Biotecnol Biomed, Bellaterra 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
CIBER Bioingenieria, Biomateri Nanomed CIBER BBN, C Monforte Lemos 3-5, Madrid 28029, Spain
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